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1.
Int J Nanomedicine ; 19: 5397-5418, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38863647

RESUMEN

Background: The healing of burn wounds is a complicated physiological process that involves several stages, including haemostasis, inflammation, proliferation, and remodelling to rebuild the skin and subcutaneous tissue integrity. Recent advancements in nanomaterials, especially nanofibers, have opened a new way for efficient healing of wounds due to burning or other injuries. Methods: This study aims to develop and characterize collagen-decorated, bilayered electrospun nanofibrous mats composed of PVP and PVA loaded with Resveratrol (RSV) and Ampicillin (AMP) to accelerate burn wound healing and tissue repair. Results: Nanofibers with smooth surfaces and web-like structures with diameters ranging from 200 to 400 nm were successfully produced by electrospinning. These fibres exhibited excellent in vitro properties, including the ability to absorb wound exudates and undergo biodegradation over a two-week period. Additionally, these nanofibers demonstrated sustained and controlled release of encapsulated Resveratrol (RSV) and Ampicillin (AMP) through in vitro release studies. The zone of inhibition (ZOI) of PVP-PVA-RSV-AMP nanofibers against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) was found 31±0.09 mm and 12±0.03, respectively, which was significantly higher as compared to positive control. Similarly, the biofilm study confirmed the significant reduction in the formation of biofilms in nanofiber-treated group against both S. aureus and E. coli. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analysis proved the encapsulation of RSV and AMP successfully into nanofibers and their compatibility. Haemolysis assay (%) showed no significant haemolysis (less than 5%) in nanofiber-treated groups, confirmed their cytocompatibility with red blood cells (RBCs). Cell viability assay and cell adhesion on HaCaT cells showed increased cell proliferation, indicating its biocompatibility as well as non-toxic properties. Results of the in-vivo experiments on a burn wound model demonstrated potential burn wound healing in rats confirmed by H&E-stained images and also improved the collagen synthesis in nanofibers-treated groups evidenced by Masson-trichrome staining. The ELISA assay clearly indicated the efficient downregulation of TNF-alpha and IL-6 inflammatory biomarkers after treatment with nanofibers on day 10. Conclusion: The RSV and AMP-loaded nanofiber mats, developed in this study, expedite burn wound healing through their multifaceted approach.


Asunto(s)
Ampicilina , Quemaduras , Colágeno , Escherichia coli , Nanofibras , Alcohol Polivinílico , Povidona , Resveratrol , Staphylococcus aureus , Cicatrización de Heridas , Resveratrol/farmacología , Resveratrol/química , Resveratrol/administración & dosificación , Resveratrol/farmacocinética , Nanofibras/química , Quemaduras/tratamiento farmacológico , Cicatrización de Heridas/efectos de los fármacos , Animales , Colágeno/química , Povidona/química , Staphylococcus aureus/efectos de los fármacos , Alcohol Polivinílico/química , Humanos , Escherichia coli/efectos de los fármacos , Ampicilina/farmacología , Ampicilina/química , Ampicilina/farmacocinética , Ampicilina/administración & dosificación , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Ratas , Biopelículas/efectos de los fármacos , Masculino
2.
Int J Nanomedicine ; 19: 5681-5703, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38882541

RESUMEN

Introduction: Diabetes mellitus is frequently associated with foot ulcers, which pose significant health risks and complications. Impaired wound healing in diabetic patients is attributed to multiple factors, including hyperglycemia, neuropathy, chronic inflammation, oxidative damage, and decreased vascularization. Rationale: To address these challenges, this project aims to develop bioactive, fast-dissolving nanofiber dressings composed of polyvinylpyrrolidone loaded with a combination of an antibiotic (moxifloxacin or fusidic acid) and anti-inflammatory drug (pirfenidone) using electrospinning technique to prevent the bacterial growth, reduce inflammation, and expedite wound healing in diabetic wounds. Results: The fabricated drug-loaded fibers exhibited diameters of 443 ± 67 nm for moxifloxacin/pirfenidone nanofibers and 488 ± 92 nm for fusidic acid/pirfenidone nanofibers. The encapsulation efficiency, drug loading and drug release studies for the moxifloxacin/pirfenidone nanofibers were found to be 70 ± 3% and 20 ± 1 µg/mg, respectively, for moxifloxacin, and 96 ± 6% and 28 ± 2 µg/mg, respectively, for pirfenidone, with a complete release of both drugs within 24 hours, whereas the fusidic acid/pirfenidone nanofibers were found to be 95 ± 6% and 28 ± 2 µg/mg, respectively, for fusidic acid and 102 ± 5% and 30 ± 2 µg/mg, respectively, for pirfenidone, with a release rate of 66% for fusidic acid and 80%, for pirfenidone after 24 hours. The efficacy of the prepared nanofiber formulations in accelerating wound healing was evaluated using an induced diabetic rat model. All tested formulations showed an earlier complete closure of the wound compared to the controls, which was also supported by the histopathological assessment. Notably, the combination of fusidic acid and pirfenidone nanofibers demonstrated wound healing acceleration on day 8, earlier than all tested groups. Conclusion: These findings highlight the potential of the drug-loaded nanofibrous system as a promising medicated wound dressing for diabetic foot applications.


Asunto(s)
Antibacterianos , Vendajes , Pie Diabético , Liberación de Fármacos , Ácido Fusídico , Moxifloxacino , Nanofibras , Piridonas , Cicatrización de Heridas , Pie Diabético/tratamiento farmacológico , Pie Diabético/terapia , Nanofibras/química , Animales , Moxifloxacino/administración & dosificación , Moxifloxacino/farmacología , Moxifloxacino/química , Moxifloxacino/farmacocinética , Cicatrización de Heridas/efectos de los fármacos , Antibacterianos/química , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Piridonas/química , Piridonas/farmacología , Piridonas/farmacocinética , Piridonas/administración & dosificación , Ácido Fusídico/administración & dosificación , Ácido Fusídico/farmacología , Ácido Fusídico/química , Ácido Fusídico/farmacocinética , Ratas , Masculino , Diabetes Mellitus Experimental , Povidona/química , Ratas Sprague-Dawley
3.
AAPS PharmSciTech ; 25(5): 134, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862663

RESUMEN

Inclusion complexes require higher concentration of Beta cyclodextrins (ßCD) resulting in increased formulation bulk, toxicity, and production costs. This systematic review offers a comprehensive analysis using Quality by design (QbD) as a tool to predict potential applications of Polyvinylpyrrolidone (PVP) as a ternary substance to address issues of inclusion complexes. We reviewed 623 documents from 2013 to 2023 and Eighteen (18) research papers were selected for statistical and meta-analysis using the QbD concept to identify the most critical factors for selecting drugs and effect of PVP on inclusion complexes. The QbD analysis revealed that Molecular weight (MW), Partition coefficient (Log P), and the auxiliary substance ratio directly affected complexation efficiency (CE), thermodynamic stability in terms of Gibbs free energy (ΔG), and percent drug release. However, Stability constant (Ks) remained unaffected by any of these parameters. The results showed that low MW (250), median Log P (6), and a ßCD: PVP ratio of 2:3 would result in higher CE, lower G, and improved drug release. PVP improves drug solubility, enhances delivery and therapeutic outcomes, and counteracts increased drug ionization due to decreased pH. In certain cases, its bulky nature and hydrogen bonding with CD molecules can form non-inclusion complexes. The findings of the study shows that there is potential molecular interaction between PVP and ß-cyclodextrins, which possibly enhances the stability of inclusion complexes for drug with low MW and log P values less than 9. The systematic review shows a comprehensive methodology based on QbD offers a replicable template for future investigations into drug formulation research.


Asunto(s)
Ciclodextrinas , Povidona , Solubilidad , beta-Ciclodextrinas , beta-Ciclodextrinas/química , Química Farmacéutica/métodos , Ciclodextrinas/química , Liberación de Fármacos , Excipientes/química , Peso Molecular , Proyectos Piloto , Povidona/química , Termodinámica
4.
PLoS One ; 19(6): e0303900, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38843120

RESUMEN

BACKGROUND: Candesartan cilexetil (CC) is a selective angiotensin II receptor antagonist widely used to treat hypertension. CC is a substrate of P-glycoprotein (P-gp), causing its efflux to the intestinal lumen. It is also practically insoluble in water and has low oral bioavailability (14%). Thus, the current study aims to improve the in vitro dissolution of CC by developing solid dispersion systems (SDSs) and corroborating the in vitro results using a simulated pharmacokinetics study. METHODS: The SDSs were prepared using polyvinyl pyrrolidone (PVP) as a water-soluble polymer, Eudragit E100 (EE100) as a pH-dependent soluble carrier, and a combination of these two polymers. The saturation solubility and the dissolution rate studies of the prepared systems in three dissolution media were performed. The optimized system SE-EE5 was selected for further investigations, including DSC, XRD, FTIR, FESEM, DLS, TSEM, IVIVC convolution study, and stability studies. RESULTS: The solubility of CC significantly increased by a factor of 27,037.344 when formulated as a solid dispersion matrix using EE100 at a ratio of 1:5 (w/w) drug to polymer (SE-EE5 SD), compared to the solubility of the pure drug. The mechanism of solubility and dissolution rate enhancement of CC by the optimized SDS was found to be via the conversion of the crystalline CC into the amorphous form as well as nanoparticles formation upon dissolution at a pH below 5. The instrumental analysis tests showed good compatibility between CC and EE100 and there was no chemical interaction between the drug and the polymer. Moreover, the stability tests confirmed that the optimized system was stable after three months of storage at 25°C. CONCLUSION: The utilization of the solid dispersion technique employing EE 100 polymer as a matrix demonstrates significant success in enhancing the solubility, dissolution, and subsequently, the bioavailability of water-insoluble drugs like CC.


Asunto(s)
Bencimidazoles , Compuestos de Bifenilo , Polímeros , Solubilidad , Tetrazoles , Bencimidazoles/química , Bencimidazoles/farmacocinética , Tetrazoles/química , Tetrazoles/farmacocinética , Compuestos de Bifenilo/química , Compuestos de Bifenilo/farmacocinética , Polímeros/química , Polímeros/farmacocinética , Povidona/química , Agua/química , Concentración de Iones de Hidrógeno , Disponibilidad Biológica , Estabilidad de Medicamentos , Liberación de Fármacos , Acrilatos
5.
Int J Mol Sci ; 25(11)2024 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-38892328

RESUMEN

Curcumin is a natural compound that is considered safe and may have potential health benefits; however, its poor stability and water insolubility limit its therapeutic applications. Different strategies aim to increase its water solubility. Here, we tested the compound PVP-curcumin as a photosensitizer for antimicrobial photodynamic therapy (aPDT) as well as its potential to act as an adjuvant in antibiotic drug therapy. Gram-negative E. coli K12 and Gram-positive S. capitis were subjected to aPDT using various PVP-curcumin concentrations (1-200 µg/mL) and 475 nm blue light (7.5-45 J/cm2). Additionally, results were compared to aPDT using 415 nm blue light. Gene expression of recA and umuC were analyzed via RT-qPCR to assess effects on the bacterial SOS response. Further, the potentiation of Ciprofloxacin by PVP-curcumin was investigated, as well as its potential to prevent the emergence of antibiotic resistance. Both bacterial strains were efficiently reduced when irradiated with 415 nm blue light (2.2 J/cm2) and 10 µg/mL curcumin. Using 475 nm blue light, bacterial reduction followed a biphasic effect with higher efficacy in S. capitis compared to E. coli K12. PVP-curcumin decreased recA expression but had limited effect regarding enhancing antibiotic treatment or impeding resistance development. PVP-curcumin demonstrated effectiveness as a photosensitizer against both Gram-positive and Gram-negative bacteria but did not modulate the bacterial SOS response.


Asunto(s)
Antibacterianos , Ciprofloxacina , Curcumina , Fármacos Fotosensibilizantes , Rec A Recombinasas , Curcumina/farmacología , Fármacos Fotosensibilizantes/farmacología , Rec A Recombinasas/metabolismo , Rec A Recombinasas/genética , Ciprofloxacina/farmacología , Antibacterianos/farmacología , Fotoquimioterapia/métodos , Respuesta SOS en Genética/efectos de los fármacos , Escherichia coli K12/efectos de los fármacos , Escherichia coli K12/genética , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Povidona/química , Povidona/farmacología , Pruebas de Sensibilidad Microbiana , Escherichia coli/efectos de los fármacos , Luz , Proteínas de Unión al ADN
6.
Carbohydr Polym ; 341: 122348, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38876718

RESUMEN

Antibiotic abuse is increasing the present rate of drug-resistant bacterial wound infections, producing a significant healthcare burden globally. Herein, we prepared a pH-responsive CMCS/PVP/TA (CPT) multifunctional hydrogel dressing by embedding the natural plant extract TA as a nonantibiotic and cross-linking agent in carboxymethyl chitosan (CMCS) and polyvinylpyrrolidone (PVP) to prompt wound healing. The CPT hydrogel demonstrated excellent self-healing, self-adaptive, and adhesion properties to match different wound requirements. Importantly, this hydrogel showed pH sensitivity and exhibited good activity against resistant bacteria and antioxidant activity by releasing TA in case of bacterial infection (alkaline). Furthermore, the CPT hydrogel exhibited coagulant ability and could rapidly stop bleeding within 30 s. The biocompatible hydrogel effectively accelerated wound healing in a full-thickness skin defect model by thickening granulation tissue, increasing collagen deposition, vascular proliferation, and M2-type macrophage polarization. In conclusion, this study demonstrates that multifunctional CPT hydrogel offers a candidate material with potential applications for infected skin wound healing.


Asunto(s)
Antibacterianos , Vendajes , Quitosano , Hidrogeles , Cicatrización de Heridas , Quitosano/química , Quitosano/análogos & derivados , Quitosano/farmacología , Quitosano/síntesis química , Cicatrización de Heridas/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Hidrogeles/síntesis química , Animales , Concentración de Iones de Hidrógeno , Ratones , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Povidona/química , Masculino , Staphylococcus aureus/efectos de los fármacos , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/síntesis química , Piel/efectos de los fármacos , Piel/patología
7.
Molecules ; 29(11)2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38893548

RESUMEN

The present work deals with the sol-gel synthesis of silica-poly (vinylpyrrolidone) hybrid materials. The nanohybrids (Si-PVP) have been prepared using an acidic catalyst at ambient temperature. Tetramethyl ortosilane (TMOS) was used as a silica precursor. Poly (vinylpyrrolidone) (PVP) was introduced into the reaction mixture as a solution in ethanol with a concentration of 20%. The XRD established that the as-prepared material is amorphous. The IR and 29Si MAS NMR spectra proved the formation of a polymerized silica network as well as the hydrogen bonding interactions between the silica matrix and OH hydrogens of the silanol groups. The TEM showed spherical particle formation along with increased agglomeration tendency. The efficacy of SiO2/PVP nanoparticles as a potential antimicrobial agent against a wide range of bacteria was evaluated as bacteriostatic, using agar diffusion and spot tests. Combined effects of hybrid nanomaterial and antibiotics could significantly reduce the bactericidal concentrations of both the antibiotic and the particles, and they could also eliminate the antibiotic resistance of the pathogen. The registered prooxidant activity of the newly synthesized material was confirmative and explicatory for the antibacterial properties of the tested substance and its synergetic combination with antibiotics. The effect of new hybrid material on Crustacea Daphnia magna was also estimated as harmless under concentration of 0.1 mg/mL.


Asunto(s)
Antibacterianos , Povidona , Dióxido de Silicio , Dióxido de Silicio/química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Povidona/química , Pruebas de Sensibilidad Microbiana , Nanopartículas/química , Transición de Fase , Bacterias/efectos de los fármacos
8.
Eur J Pharm Sci ; 198: 106780, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38697312

RESUMEN

Co-milling is an effective technique for improving dissolution rate limited absorption characteristics of poorly water-soluble drugs. However, there is a scarcity of models available to forecast the magnitude of dissolution rate improvement caused by co-milling. Therefore, this study endeavoured to quantitatively predict the increase in dissolution by co-milling based on drug properties. Using a biorelevant dissolution setup, a series of 29 structurally diverse and crystalline drugs were screened in co-milled and physically blended mixtures with Polyvinylpyrrolidone K25. Co-Milling Dissolution Ratios after 15 min (COMDR15 min) and 60 min (COMDR60 min) drug release were predicted by variable selection in the framework of a partial least squares (PLS) regression. The model forecasts the COMDR15 min (R2 = 0.82 and Q2 = 0.77) and COMDR60 min (R2 = 0.87 and Q2 = 0.84) with small differences in root mean square errors of training and test sets by selecting four drug properties. Based on three of these selected variables, applicable multiple linear regression equations were developed with a high predictive power of R2 = 0.83 (COMDR15 min) and R2 = 0.84 (COMDR60 min). The most influential predictor variable was the median drug particle size before milling, followed by the calculated drug logD6.5 value, the calculated molecular descriptor Kappa 3 and the apparent solubility of drugs after 24 h dissolution. The study demonstrates the feasibility of forecasting the dissolution rate improvements of poorly water-solube drugs through co-milling. These models can be applied as computational tools to guide formulation in early stage development.


Asunto(s)
Composición de Medicamentos , Liberación de Fármacos , Solubilidad , Composición de Medicamentos/métodos , Povidona/química , Simulación por Computador , Preparaciones Farmacéuticas/química , Análisis de los Mínimos Cuadrados
9.
Int J Pharm ; 658: 124180, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38705246

RESUMEN

During the past several decades, nanostructures have played their increasing influences on the developments of novel nano drug delivery systems, among which, double-chamber Janus nanostructure is a popular one. In this study, a new tri-channel spinneret was developed, in which two parallel metal capillaries were nested into another metal capillary in a core-shell manner. A tri-fluid electrospinning was conducted with a solvent mixture as the shell working fluid for ensuring the formation of an integrated Janus nanostructure. The scanning electronic microscopic results demonstrated that the resultant nanofibers had a linear morphology and two distinct compartments within them, as indicated by the image of a cross-section. Fourier Transformation Infra-Red spectra and X-Ray Diffraction patterns verified that the loaded poorly water-soluble drug, i.e. icariin, presented in the Janus medicated nanofibers in an amorphous state, which should be attributed to the favorable secondary interactions between icariin and the two soluble polymeric matrices, i.e. hydroxypropyl methyl cellulose (HPMC) and polyvinylpyrrolidone (PVP). The in vitro dissolution tests revealed that icariin, when encapsulated within the Janus nanofibers, exhibited complete release within a duration of 5 min, which was over 11 times faster compared to the raw drug particles. Furthermore, the ex vivo permeation tests demonstrated that the permeation rate of icariin was 16.2 times higher than that of the drug powders. This improvement was attributed to both the rapid dissolution of the drug and the pre-release of the trans-membrane enhancer sodium lauryl sulfate from the PVP side of the nanofibers. Mechanisms for microformation, drug release, and permeation were proposed. Based on the methodologies outlined in this study, numerous novel Janus nanostructure-based nano drug delivery systems can be developed for poorly water-soluble drugs in the future.


Asunto(s)
Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Flavonoides , Derivados de la Hipromelosa , Nanofibras , Povidona , Solventes , Nanofibras/química , Animales , Solventes/química , Povidona/química , Flavonoides/química , Flavonoides/administración & dosificación , Flavonoides/farmacocinética , Sistemas de Liberación de Medicamentos/métodos , Derivados de la Hipromelosa/química , Solubilidad , Absorción Cutánea , Masculino , Ratas
10.
Int J Pharm ; 658: 124204, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38710297

RESUMEN

Pulsatile drug delivery is hardly achieved by conventional gastro-retentive dosage forms. Artesunate as a typical anti-malaria medicine needs oral pulsatile release. Here, artesunate-loaded pulsatile-release multi-unit gastro-retentive tablets (APGTs) were prepared with a semi-solid extrusion three-dimensional (3D) printing method. An APGT was composed of three units: artesunate-loaded immediate and delayed release units and a block unit. The matrix of the immediate/delayed release units consisted of polyvinylpyrrolidone (PVP) K30 and croscarmellose sodium, which improved the rapid release of artesunate when contacting water. The block unit consisted of octadecanol, hydroxypropyl methyl cellulose K15M, PVP K30, and poloxamer F68. APGTs showed multi-phase release in simulated gastric liquids (SGLs). The first immediate release phase continued for 1 h followed by a long block phase for 7 h. The second rapid release phase was initiated when the eroded holes in the block unit extended to the inner delayed release unit, and this phase continued for about 14 h. Low-density APGTs could ensure their long-term floating in the stomach. Oral APGTs remained in the rabbit stomach for about 20 h. 3D printing provides a new strategy for the preparation of oral pulsatile-release tablets.


Asunto(s)
Antimaláricos , Artesunato , Preparaciones de Acción Retardada , Liberación de Fármacos , Povidona , Impresión Tridimensional , Comprimidos , Artesunato/administración & dosificación , Artesunato/química , Artesunato/farmacocinética , Animales , Conejos , Antimaláricos/administración & dosificación , Antimaláricos/química , Antimaláricos/farmacocinética , Povidona/química , Derivados de la Hipromelosa/química , Excipientes/química , Sistemas de Liberación de Medicamentos , Administración Oral , Carboximetilcelulosa de Sodio/química , Poloxámero/química , Mucosa Gástrica/metabolismo
11.
J Nanobiotechnology ; 22(1): 217, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38725012

RESUMEN

Excess free radicals at the wound site can cause an inflammatory response, which is not conducive to wound healing. Hydrogels with antioxidant properties can prevent inflammatory storms by scavenging free radicals from the wound site and inhibiting the release of inflammatory factors. In this study, we prepared the carboxymethyl chitosan (CMCS)/polyvinyl pyrrolidone (PVP)/Molybdenum (IV) Selenide (MoSe2), and platelet-rich plasma (PRP) (CMCS/PVP/MoSe2/PRP) hydrogels for accelerating the repair of wounds. In the hydrogels, the MoSe2 can scavenge various free radicals to reduce oxidative stress at the site of inflammation, endowed the hydrogels with antioxidant properties. Interestingly, growth factors released by PRP assisted the tissue repair by promoting the formation of new capillaries. CMCS as a backbone not only showed good biocompatibility and biodegradability but also played a significant role in maintaining the sustained release of growth factors. In addition, incorporating PVP enhanced the tissue adhesion and mechanical properties. The multifunctional composite antioxidant hydrogels have good swelling properties and biodegradability, which is completely degraded within 28 days. Thus, the antioxidant CMCS/PVP/MoSe2/PRP hydrogels provide a new idea for designing ideal multifunctional wound dressings.


Asunto(s)
Antioxidantes , Vendajes , Quitosano , Hidrogeles , Plasma Rico en Plaquetas , Povidona , Cicatrización de Heridas , Quitosano/química , Quitosano/análogos & derivados , Quitosano/farmacología , Cicatrización de Heridas/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/química , Povidona/química , Povidona/análogos & derivados , Hidrogeles/química , Hidrogeles/farmacología , Plasma Rico en Plaquetas/química , Animales , Ratones , Masculino , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Estrés Oxidativo/efectos de los fármacos , Humanos
12.
Int J Nanomedicine ; 19: 4339-4356, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38774026

RESUMEN

Background: The in vivo barriers and multidrug resistance (MDR) are well recognized as great challenges for the fulfillment of antitumor effects of current drugs, which calls for the development of novel therapeutic agents and innovative drug delivery strategies. Nanodrug (ND) combining multiple drugs with distinct modes of action holes the potential to circumvent these challenges, while the introduction of photothermal therapy (PTT) can give further significantly enhanced efficacy in cancer therapy. However, facile preparation of ND which contains dual drugs and photothermal capability with effective cancer treatment ability has rarely been reported. Methods: In this study, we selected curcumin (Cur) and doxorubicin (Dox) as two model drugs for the creation of a cocktail ND (Cur-Dox ND). We utilized polyvinylpyrrolidone (PVP) as a stabilizer and regulator to prepare Cur-Dox ND in a straightforward one-pot method. Results: The size of the resulting Cur-Dox ND can be easily adjusted by tuning the charged ratios. It was noted that both loaded drugs in Cur-Dox ND can realize their functions in the same target cell. Especially, the P-glycoprotein inhibition effect of Cur can synergistically cooperate with Dox, leading to enhanced inhibition of 4T1 cancer cells. Furthermore, Cur-Dox ND exhibited pH-responsive dissociation of loaded drugs and a robust photothermal translation capacity to realize multifunctional combat of cancer for photothermal enhanced anticancer performance. We further demonstrated that this effect can also be realized in 3D multicellular model, which possibly attributed to its superior drug penetration as well as photothermal-enhanced cellular uptake and drug release. Conclusion: In summary, Cur-Dox ND might be a promising ND for better cancer therapy.


Asunto(s)
Curcumina , Doxorrubicina , Povidona , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacocinética , Povidona/química , Curcumina/química , Curcumina/farmacología , Curcumina/farmacocinética , Línea Celular Tumoral , Animales , Ratones , Humanos , Nanopartículas/química , Tamaño de la Partícula , Antineoplásicos/química , Antineoplásicos/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Terapia Fototérmica/métodos , Liberación de Fármacos , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Portadores de Fármacos/química , Supervivencia Celular/efectos de los fármacos
13.
Int J Mol Sci ; 25(10)2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38791388

RESUMEN

The use of targeted drug delivery systems, including those based on selective absorption by certain receptors on the surface of the target cell, can lead to a decrease in the minimum effective dose and the accompanying toxicity of the drug, as well as an increase in therapeutic efficacy. A fullerene C60 conjugate (FA-PVP-C60) with polyvinylpyrrolidone (PVP) as a biocompatible spacer and folic acid (FA) as a targeting ligand for tumor cells with increased expression of folate receptors (FR) was obtained. Using 13C NMR spectroscopy, FT-IR, UV-Vis spectrometry, fluorometry and thermal analysis, the formation of the conjugate was confirmed and the nature of the binding of its components was established. The average particle sizes of the conjugate in aqueous solutions and cell culture medium were determined using dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). The FA-PVP-C60 showed antiradical activity against •DPPH, •OH and O2•-, but at the same time, it was shown to generate 1O2. It was found that the conjugate in the studied concentration range (up to 200 µg/mL) is non-toxic in vitro and does not affect the cell cycle. To confirm the ability of the conjugate to selectively accumulate through folate-mediated endocytosis, its uptake into cells was analyzed by flow cytometry and confocal microscopy. It was shown that the conjugate is less absorbed by A549 cells with low FR expression than by HeLa, which has a high level of expression of this receptor.


Asunto(s)
Sistemas de Liberación de Medicamentos , Ácido Fólico , Fulerenos , Povidona , Ácido Fólico/química , Ácido Fólico/farmacología , Humanos , Povidona/química , Fulerenos/química , Fulerenos/farmacología , Sistemas de Liberación de Medicamentos/métodos , Línea Celular Tumoral , Células A549 , Células HeLa , Tamaño de la Partícula
14.
Molecules ; 29(10)2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38792144

RESUMEN

Peripheral nerve injuries (PNI) impact millions of individuals in the United States, prompting thousands of nerve repair procedures annually. Nerve conduits (NC) are commonly utilized to treat nerve injuries under 3 cm but larger gaps still pose a challenge for successful peripheral nerve regeneration (PNR) and functional recovery. This is partly attributed to the absence of bioactive agents such as stem cells or growth factors in FDA-approved conduits due to safety, harvesting, and reproducibility concerns. Therefore, curcumin, a bioactive phytochemical, has emerged as a promising alternative bioactive agent due to its ability to enhance PNR and overcome said challenges. However, its hydrophobicity and rapid degradation in aqueous solutions are considerable limitations. In this work, a nanoscale delivery platform with tannic acid (TA) and polyvinylpyrrolidone (PVP) was developed to encapsulate curcumin for increased colloidal and chemical stability. The curcumin nanoparticles (CurNPs) demonstrate significantly improved stability in water, reduced degradation rates, and controlled release kinetics when compared to free curcumin. Further, cell studies show that the CurNP is biocompatible when introduced to neuronal cells (SH-SY5Y), rat Schwann cells (RSC-S16), and murine macrophages (J774 A.1) at 5 µM, 5 µM, and 10 µM of curcumin, respectively. As a result of these improved physicochemical properties, confocal fluorescence microscopy revealed superior delivery of curcumin into these cells when in the form of CurNPs compared to its free form. A hydrogen peroxide-based oxidative stress study also demonstrated the CurNP's potential to protect J774 A.1 cells against excessive oxidative stress. Overall, this study provides evidence for the suitability of CurNPs to be used as a bioactive agent in NC applications.


Asunto(s)
Curcumina , Nanopartículas , Curcumina/farmacología , Curcumina/química , Animales , Ratas , Nanopartículas/química , Ratones , Humanos , Sistemas de Liberación de Medicamentos , Regeneración Nerviosa/efectos de los fármacos , Polímeros/química , Células de Schwann/efectos de los fármacos , Liberación de Fármacos , Taninos/química , Taninos/farmacología , Línea Celular , Estrés Oxidativo/efectos de los fármacos , Povidona/química
15.
Analyst ; 149(11): 3078-3084, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38717228

RESUMEN

This study is the first to identify bovine blastocysts through in vitro fertilization (IVF) of matured oocytes with a large quantity of high-quality sperm separated from a biomimetic cervix environment. We obtained high-quality sperm in large quantities using an IVF sperm sorting chip (SSC), which could mimic the viscous environment of the bovine cervix during ovulation and facilitates isolation of progressively motile sperm from semen. The viscous environment-on-a-chip was realized by formulating and implementing polyvinylpyrrolidone (PVP)-based solutions for the SSC medium. Sperm separated from the IVF-SSC containing PVP 1.5% showed high motility, normal morphology and high DNA integrity. As a result of IVF, a higher rate of hatching blastocysts, which is the pre-implantation stage, were observed, compared to the conventional swim-up method. Our results may significantly contribute to improving livestock with superior male and female genetic traits, thus overcoming the limitation of artificial insemination based on the superior genetic traits of existing males.


Asunto(s)
Desarrollo Embrionario , Fertilización In Vitro , Espermatozoides , Animales , Bovinos , Masculino , Espermatozoides/citología , Espermatozoides/química , Femenino , Fertilización In Vitro/métodos , Desarrollo Embrionario/fisiología , Biomimética/métodos , Cuello del Útero/citología , Povidona/química , Blastocisto/citología , Motilidad Espermática/efectos de los fármacos
16.
Sci Rep ; 14(1): 10679, 2024 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724534

RESUMEN

The supercritical antisolvent (SAS) process was a green alternative to improve the low bioavailability of insoluble drugs. However, it is difficult for SAS process to industrialize with limited production capacity. A coaxial annular nozzle was used to prepare the microcapsules of aprepitant (APR) and polyvinylpyrrolidone (PVP) by SAS with N, N-Dimethylformamide (DMF) as solvent. Meanwhile, the effects of polymer/drug ratio, operating pressure, operating temperature and overall concentration on particles morphology, mean particle diameter and size distribution were analyzed. Microcapsules with mean diameters ranging from 2.04 µm and 9.84 µm were successfully produced. The morphology, particle size, thermal behavior, crystallinity, drug content, drug dissolution and residual amount of DMF of samples were analyzed. The results revealed that the APR drug dissolution of the microcapsules by SAS process was faster than the unprocessed APR. Furthermore, the drug powder collected every hour is in the kilogram level, verifying the possibility to scale up the production of pharmaceuticals employing the SAS process from an industrial point of view.


Asunto(s)
Aprepitant , Cápsulas , Tamaño de la Partícula , Povidona , Solventes , Cápsulas/química , Povidona/química , Solventes/química , Aprepitant/química , Solubilidad , Dimetilformamida/química , Liberación de Fármacos , Composición de Medicamentos/métodos , Temperatura
17.
Sci Total Environ ; 935: 173428, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-38777065

RESUMEN

The water-soluble polymer polyvinylpyrrolidone (PVP) is an established ingredient in pharmaceutical and personal care product (PPCP) formulations. Due to its high usage and lack of biodegradability, it has been detected up to 7.0 mg L-1 in wastewater and 0.1 mg L-1 in the receiving freshwaters, with several studies showing detrimental sublethal effects in a range of aquatic species. A lack of simple analytical methods to detect and quantify PVP currently impacts further investigation into the cause of these sublethal effects. In this paper we propose a refractive index gel-permeation chromatography (GPC) method to quantify PVP, which includes the processing of raw chromatograms using line deconvolution to calculate peak area. The method was then applied to Daphnia magna exposed to PVP for 48 h. A limit of detection (LOD) and limit of quantification (LOQ) of 0.05 and 0.2 mg mL-1 respectively was determined, with a recovery of 78 % from spiked Daphnia magna. PVP was detected in the samples above the LOD but below the LOQ. This suggests PVP is ingested by Daphnia magna, which warrants further investigation into whether bioaccumulation of PVP could be causing the sublethal effects seen in other studies.


Asunto(s)
Daphnia , Povidona , Contaminantes Químicos del Agua , Animales , Daphnia/fisiología , Daphnia/efectos de los fármacos , Povidona/química , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad , Refractometría , Monitoreo del Ambiente/métodos , Organismos Acuáticos/efectos de los fármacos , Límite de Detección , Polímeros , Daphnia magna
18.
Environ Res ; 252(Pt 3): 119068, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38705452

RESUMEN

Cellulose acetate membranes exhibit a potential to be applied in hemodialysis. However, their performance is limited by membrane fouling and a lack of antibacterial properties. In this research, copper oxide (I) nanoparticles were fabricated in situ into a cellulose acetate matrix in the presence of polyvinylpyrrolidone (pore-forming agent) and sulfobetaine (stabilising agent) to reduce the leakage of copper ions from nano-enhanced membranes. The influence of nanoparticles on the membrane structure and their antibacterial and antifouling properties were investigated. The results showed that incorporating Cu2O NPs imparted significant antibacterial properties against Staphylococcus aureus and fouling resistance under physiological conditions. The Cu2O NPs-modified membrane could pave the way for potential dialysis applications.


Asunto(s)
Antibacterianos , Incrustaciones Biológicas , Celulosa , Cobre , Membranas Artificiales , Staphylococcus aureus , Celulosa/análogos & derivados , Celulosa/química , Celulosa/farmacología , Cobre/química , Antibacterianos/farmacología , Antibacterianos/química , Staphylococcus aureus/efectos de los fármacos , Incrustaciones Biológicas/prevención & control , Nanopartículas/química , Nanopartículas del Metal/química , Povidona/química , Povidona/análogos & derivados
19.
Chem Biol Interact ; 396: 111064, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38768772

RESUMEN

Flavonoids are considered as health-protecting food constituents. The testing of their biological effects is however hampered by their low oral absorption and complex metabolism. In order to investigate the direct effect(s) of unmetabolized flavonoid, a preparation in a biologically friendly solvent for intravenous administration is needed. Isorhamnetin, a natural flavonoid and a human metabolite of the most frequently tested flavonoid quercetin, has very low water solubility (<3.5 µg/mL). The aim of this study was to improve its solubility to enable intravenous administration and to test its pharmacokinetics in an animal model. By using polyvinylpyrrolidone (PVP10) and benzalkonium chloride, we were able to improve the solubility approximately 600 times to 2.1 mg/mL. This solution was then administered intravenously at a dose of 0.5 mg/kg of isorhamnetin to rats and its pharmacokinetics was analyzed. The pharmacokinetics of isorhamnetin corresponded to two compartmental model with a rapid initial distribution phase (t1/2α: 5.7 ± 4.3 min) and a slower elimination phase (t1/2ß: 61 ± 47.5 min). Two sulfate metabolites were also identified. PVP10 and benzalkonium did not modify the properties of isorhamnetin (iron chelation and reduction, and cell penetration) substantially. In conclusion, the novel preparation reported in this study is suitable for future testing of isorhamnetin effects under in vivo conditions.


Asunto(s)
Administración Intravenosa , Povidona , Quercetina , Solubilidad , Agua , Animales , Quercetina/farmacocinética , Quercetina/análogos & derivados , Quercetina/administración & dosificación , Quercetina/química , Ratas , Masculino , Agua/química , Povidona/química , Compuestos de Benzalconio/farmacocinética , Compuestos de Benzalconio/química , Ratas Wistar
20.
Int J Biol Macromol ; 270(Pt 2): 132161, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38723810

RESUMEN

A novel magnetic polyvinylpyrrolidone/chitosan-Schiff base/Fe2O3 (PVP/CS-SB/Fe2O3) adsorbent was prepared by one-pot facile co-precipitation route for adsorption of Pb(II) and Hg(II) ions from aqueous solution. Fourier transform infrared-spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscope (SEM), vibrating sample magnetometer (VSM) and Brunauer-Emmett-Teller (BET) were used to characterize the synthesized PVP/CS-SB/Fe2O3. The results predicted that the successfully synthesis of magnetic CSSB-PVP@Fe2O3. The effects of important factors such as pH solution, contact time, concentration of metal ions, adsorbent dose and co-existing ions on Pb(II) and Hg(II) adsorption were investigated. The maximum adsorption capacities of Pb(II) and Hg(II) ions at optimal conditions were 120 mg/g and 102.5 mg/g, respectively. The kinetic studies predicted that the adsorption followed the pseudo-second-order (PSO) model as chemisorption using the coordination of active sites of PVP/CS-SB/Fe2O3 with the metal ions and also n-π interactions. Reproducibility results predicted that the excellent regeneration ability after 6 adsorption cycles. According to the results of this work, the PVP/CS-SB/Fe2O3 nanocomposite is promising for Pb(II) and Hg(II) ions adsorption and can be potential as a simple, low-cost, high-efficient adsorbent for decontamination of other heavy metal ions from aqueous solution.


Asunto(s)
Quitosano , Compuestos Férricos , Plomo , Mercurio , Nanocompuestos , Povidona , Bases de Schiff , Contaminantes Químicos del Agua , Purificación del Agua , Quitosano/química , Nanocompuestos/química , Adsorción , Bases de Schiff/química , Plomo/química , Plomo/aislamiento & purificación , Mercurio/química , Mercurio/aislamiento & purificación , Povidona/química , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/aislamiento & purificación , Compuestos Férricos/química , Concentración de Iones de Hidrógeno , Purificación del Agua/métodos , Cinética , Soluciones , Iones/química , Agua/química , Espectroscopía Infrarroja por Transformada de Fourier
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